Enantioselective and Diastereoselective Formation ofsyn-3-Hydroxy-4-amino Acids (syn-Statines) via Tetramic Acids

Symplocin A, a Linear Peptide from the Bahamian Cyanobacterium Symploca sp. Configurational Analysis of N,N-Dimethylamino Acids by Chiral-Phase HPLC of Naphthacyl Esters

“…1 H NMR (300 MHz, CDCl 3 ) δ 4.40 (1H, m), 3.28 (1H, d, J = 18.9 Hz), 3.16 (1H, d, J = 18.9 Hz), 1.87–2.01 (1H, m), 1.56 (9H, s), 1.1–1.4 (1H, m), 0.95 (6H, d, J = 6 Hz) in agreement with literature values. ix …”

“…The organic solution was washed with 5% aq NaHCO 3 (3 × 3 mL). The crude product was then purified by flash chromatography (silica, gradient 3:1 EtOAc/hexane to EtOAc) to yield known 4-hydroxypyrrolidinone 4a ix (55.5 mg, 30% yield). 1 H NMR (400 MHz, DMSO) δ 5.29 (1H, d, 9.66), 4.30 (1H, m), 4.00 (1H, m), 2.45 (2H, dq, J = 16.8, 6.9), 1.72 (2H, m), 1.44 (9H, s), 0.90 (6H, m), in agreement with literature values.…”

“…1 H NMR (400 MHz, DMSO) δ 5.29 (1H, d, 9.66), 4.30 (1H, m), 4.00 (1H, m), 2.45 (2H, dq, J = 16.8, 6.9), 1.72 (2H, m), 1.44 (9H, s), 0.90 (6H, m), in agreement with literature values. ix …”

“…Two diastereomers of statine were prepared by modifications of published procedures from Schmidt ix and Galeotti x (Scheme 2). ( S )- N -Boc-Leu underwent intermolecular couplingcyclization with Meldrum’s acid (DCC, DMAP) to produce the corresponding pyrrolidin-2,4-dione xi which was reduced (NaBH 4 ) diastereoselectively to provide the 4-hydroxypyrrolidinone (4 S ,5 S )- 4a (pyrrole numbering) as a single diastereomer.…”

Transannular Rearrangement of Activated Lactams: Stereoselective Synthesis of Substituted Pyrrolidine‐2,4‐diones from Diketopiperazines

“…Analogous structures to those of the pyrrolidine-2,4-dione derivatives are present in various natural and synthetic compounds, such as ascorbic acid, [2,3] which displays a broad range of well-known biological properties, and tetramic acid, [4] which exhibits antibacterial and antiviral activities. Furthermore, pyrrolidine-2,4-diones serve as significant intermediates in the synthesis of statins, [5][6][7][8][9][10][11] a key structural motif found in peptidomimetic inhibitors of proteases, such as aspartic proteases. [13,14] Owing to the lack of a general synthetic route to 3-amino, 3-alkyl derivatives of pyrrolidine-2,4-diones, the absence of a stereoselective pathway to these compounds, [15][16][17][18] and the significance of such pharmacophore moieties, we became interested in developing a stereoselective ring contraction of bis(N-tert-butoxycarbonyl)-DKPs (bis-Boc-DKPs) into pyrrolidine-2,4-diones.…”